A case series of intestinal adenomatous polyposis of unidentified etiology; a late effect of irradiation?

Abstract

BackgroundIn a large number of patients with multiple gastrointestinal adenomatous polyps, no causal germline mutation can be found. Non-genetic factors may contribute to the development of adenomatous polyps in these unexplained polyposis patients.In the development of gastrointestinal cancer, prior exposure to abdominal radiotherapy has been identified as such a factor, as it increases the gastrointestinal cancer risk in cancer survivors. A relationship of radiotherapy with intestinal polyposis, however, has not yet been described. Despite the increased cancer risk, these cancer survivors do not receive gastrointestinal screening recommendations. This case series describes three patients with adenomatous polyposis after abdominal radiotherapy.Case presentationPatient 1 was diagnosed with testicular cancer at the age of 31 and was treated with hemicastration, radiotherapy and chemotherapy. Thirty-nine years later, he was diagnosed with more than 30 colonic adenomas. Additionally, gastroduodenoscopy revealed a well-differentiated adenocarcinoma in the antrum of the stomach.Patient 2 was diagnosed with a nephroblastoma at the age of 10, which was resected and treated with radiotherapy and chemotherapy. At age 36, a rectal adenocarcinoma was diagnosed and treated by radiotherapy and a total mesorectal excision. During 11 years of surveillance endoscopies, 21 colonic adenomas and three duodenal adenomas were detected.Patient 3 was diagnosed with Hodgkin lymphoma at the age of 20 and treated with radiotherapy, followed by chemotherapy for a recurrence 3 years later. At age 62, a subtotal colectomy was performed because of colonic polyposis: 36 adenomas were detected. During screening gastro-duodenoscopy, three duodenal adenomas were detected.In all three patients, germline analysis did not reveal a mutation in the APC and MYH genes. The gastric and rectal cancer were both microsatellite stable.ConclusionThis report describes three patients with adenomatous polyposis, of which two developed a gastrointestinal cancer. The polyposis was not explained by a germline mutation in APC or MYH and all patients received abdominal radiotherapy. Although an etiologic role has not been established, an association between radiotherapy and intestinal adenomatous polyposis and the subsequent development of cancer seems very likely in our patients.

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

“…When considering more intensive CRC surveillance in HL survivors we must realise, however, that we do not know whether the pathogenesis of treatment-induced CRC in HL survivors is similar to that of CRC in the general population. As in the general population, most CRCs among HL survivors were adenocarcinomas and it appears that treatment-induced CRCs are preceded by adenomas as well ( Rigter et al , 2016 ; Rigter et al , 2017 ). Currently, most screening guidelines for HL survivors do not yet include CRC screening.…”

Therapy-Associated Polyposis, Late Presentation of a Childhood-Treated Disease

“…Advanced endoscopic techniques have the advantage of avoiding major abdominal surgery and bowel loss, especially in those with previous abdominal radiotherapy. The Dutch series 17 recommended surveillance colonoscopy of all HL patients no later than 40 years or 10 years after HL treatment, to be repeated every 5 years if negative, adjusting intervals based on findings. The 2018 Children's Oncology Group guidelines recommend colonoscopy for these survivors who received abdominopelvic radiotherapy either at age 30 or 5 years after radiotherapy, 11 then continue every 5 years.…”

Colorectal Cancer Risk and Recommendations for Colorectal Cancer Surveillance in Adult Survivors of Childhood Cancer

“…All patients received radiation and chemotherapy, and 2 were also found to have duodenal adenomas. 42 A multicenter US study identified 34 patients with therapy-associated polyposis, of which 22 (65%) did not have pathogenic variants on multigene panel testing. Of all, 10/34 (29%) only had single-gene testing, and 2/34 did not get tested.…”

“…The third patient was treated for Hodgkin Lymphoma at age 20, and at age 62 underwent subtotal colectomy for 36 detected colonic adenomas. All patients received radiation and chemotherapy, and 2 were also found to have duodenal adenomas 42…”